sing the antidote flumazenil to treat coma following unintentional drug overdose

Phase 2

• Conditions: Benzodiazepine overdose; Injury, Occupational Diseases, Poisoning

• Registration Number: ISRCTN14373275
• Lead Sponsor: niversity of Edinburgh

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-08
• Last Update Posted: 2 September 2024
• Study Completion: 2028-07-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 635

Inclusion Criteria

1. Acute suspected unintentional BZD overdose presenting to hospital with reduced consciousness after administration of clinically adequate doses of naloxone. Mixed overdoses suspected to include BZDs will be included
2. Other common causes of reduced consciousness (such as hypoglycaemia) will have been excluded
3. RASS score of -5 (unrousable) to -3 (moderate sedation)
4. Aged, or believed to be aged, 16 years and over

Exclusion Criteria

1. RASS score above -3
2. Past medical history of epilepsy or chronic brain injury
3. Seizure pre-hospital following the overdose or after hospital admission, before recruitment
4. Clinically apparent pregnancy or medical record of current pregnancy (urine-HCG test not practicable in patients with reduced consciousness)
5. Prolonged QRS duration (>120 msec, unless due to pre-existing bundle branch block) on electrocardiogram
6. Prisoner or under arrest
7. Currently detained under the Mental Health Act
8. HIV positive with detectable virus load, or no virus load data from previous 12 months, or not currently on therapy
9. Patients who have previously participated in the study (according to the recruitment log).

In Stage 1, as we explore the safety of flumazenil, we will have additional exclusion criteria to further reduce the risk of seizures.
10. No access to medical records at recruitment
11. Unknown patient (precluding use of medical records).

To ensure external validity for future clinical practice, when medical records will usually not be immediately available, these will not be used once stage 1 has identified potentially safe doses. The risk of seizures in these patients with a dose found to be safe in Stage 1 is likely to be outweighed by the chance of benefit if used pre-hospital in future.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Stage 1<br>Primary Endpoint (safety)<br>The occurrence of a tonic-clonic seizure as measured by visual observation of the participant by an experienced clinician up to 1 h after drug administration<br><br>Primary Endpoint (efficacy)<br>The level of sedation as measured using the Richmond Agitation-Sedation Score (RASS) score is in the -2 [light sedation] to 0 [alert, calm] range at 15 min after drug administration<br><br>Stage 2<br>Primary Endpoint (efficacy)<br>The level of sedation as measured using the Richmond Agitation-Sedation Score (RASS) score is in the -2 [light sedation] to 0 [alert, calm] range at 15 min after drug administration<br><br>Stage 3<br>Primary Endpoint (safety)<br>The occurrence of a tonic-clonic seizure as measured by visual observation of the participant by an experienced clinician up to 1 h after drug administration